1. Field of the Invention
This invention relates to an additive preparation, the method of making the additive preparation and the method of using the additive preparation. The additive preparation is most particularly for use in blood collection devices wherein the additive preparation comes in contact with a blood specimen that has been previously treated with heparin. The additive preparation desirably comprises a formulation comprising heparinase and a carbohydrate. The additive formulation is desirably spray dried onto the inner wall of a blood collection device. In particular, the additive formulation of the present invention exhibits stability even when subjected to gamma irradiation.
2. Description of Related Art
Heparin is an anticoagulant that is used in surgical procedures and dialysis therapy to prevent clotting in intravenous lines and in the treatment of thrombolytic disorders. It affects thrombin activity by catalyzing the action of antithrombin III (ATIII), thereby preventing the conversion of fibrinogen to fibrin which results in clotting inhibition.
Heparin is also applied to a variety of clinical situations in addition to its use as an anticoagulant. It is used in hemodialysis treatments to prevent the blood from clotting during dialysis and as an antithrombotic agent in the treatment of deep venous thrombosis and orthopedic surgery. As a prophylactic of thrombosis, it is used in conjunction with prolonged intermittent intravenous administration of drugs and fluids. Recently, heparin also has been used in fibrinolytic therapy where it is co-administered with promoters of fibrin degradation such as tissue plasminogen activator, streptokinase or urokinase. Therefore, varying quantities of heparin are found in the blood of numerous hospitalized patients.
Patients receiving heparin therapy or who have been exposed to heparin through intravenous lines are frequently tested by a variety of means for the assessment of their hematological status, to monitor heparin therapy itself or for biochemical assays. However, the presence of heparin in blood specimens collected from heparinized patients causes several problems because the heparin interferes with clotting thereby rendering the results ambiguous or unobtainable. For biochemical assays, such problems include the prolongation of clotting and insufficient removal of fibrin thereby resulting in continual and unpredictable clot formation in specimens without added anticoagulants.
Furthermore, specimens with identifiable extended clotting times require additional handling and longer preparation times to remove or manage the heparin interference. In addition, if clots are not identified prior to assaying the specimen on an automated analyzer, clots forming within the instrument may lead to incomplete test results and/or instrument clogging. Therefore, testing accuracy is minimized, unnecessary instrument downtime may need to take place to unclog the instrument, additional specimens may need to be obtained to repeat the test and technical operator time is increased.
It is therefore desirable to resolve the heparin interference problem with a method that could expeditiously and specifically remove heparin from blood samples immediately after blood collection. The additive needed to accomplish this must function over a broad range of conditions. Such conditions include, but are not limited to, heparin being neutralized, quickly, while the additive itself, should not impart any effects on blood components over a lengthy exposure period. Furthermore, the treated samples containing heparin should give a result identical to untreated samples that have not been exposed to heparin.
Therefore, with the increasing demand for reducing turn around time and for fibrin free serum specimens there is a need to remove residual heparin from specimens collected from heparinized patients.